Amino acid dehydrogenases are enzymes that engage in the coenzyme-dependent catalysis of the reductive amination reaction of a 2-oxo acid and the reverse reaction, i.e., the oxidative deamination reaction of an amino acid. For example, amino acid dehydrogenases are known to have an industrially useful activity, e.g., the highly stereoselective production of an L-amino acid from a 2-oxo acid in the presence of ammonia and a coenzyme. L-amino acids are useful for foods and feed, and as synthesis intermediates for agrichemicals, industrial reagents, cosmetics, pharmaceuticals and the like, and are also important in organic synthesis as optical resolution agents and chiral building blocks.
Examples of amino acid dehydrogenases include phenylalanine dehydrogenase (enzyme number EC1.4.1.20) and leucine dehydrogenase (enzyme number EC1.4.1.9). Examples of microorganisms known to produce phenylalanine dehydrogenase include Rhodococcus sp. (Patent Document 1), Rhodococcus maris (Non-patent Document 1), Bacillus badius (Patent Document 2), Bacillus sphaericus (Non-patent Document 2), Microbacterium sp. (Non-patent Document 3), Thermoactinomyces intermedius (Patent Document 3), Brevibacterium sp. (Patent Document 4), and Sporosarcina ureae (Patent Document 5, Non-patent Document 4).
Amino acid dehydrogenases are classified according to differences in the types of compounds with which the enzymes readily react. For example, leucine dehydrogenase exhibits good activity for branched-chain amino acids such as L-leucine, L-valine, and L-isoleucine, short-chain straight-chain amino acids such as L-norvaline, and the corresponding 2-oxo acids, but exhibits almost no activity for aromatic amino acids such as L-phenylalanine and L-tyrosine and the corresponding 2-oxo acids. In contrast, phenylalanine dehydrogenase is known to exhibit good activity for the aforementioned aromatic amino acids and the corresponding 2-oxo acids, i.e., phenylpyruvic acid and 4-hydroxyphenylpyruvic acid. However, the phenylalanine dehydrogenases known to date exhibit a weaker activity for 2-oxo acids that have a large side chain structure, e.g., naphthylpyruvic acid and homophenylpyruvic acid, than for phenylpyruvic acid (Non-patent Document 2, Non-patent Document 3). Unnatural amino acids such as L-2-naphthylalanine and L-homophenylalanine are useful as synthesis intermediates for agrichemicals, industrial reagents, cosmetics, pharmaceuticals and the like.
Phenylalanine dehydrogenase gene expression by a transformant is known, for example, for genes originating from Rhodococcus sp. (Non-patent Document 5), Bacillus badius (Non-patent Document 6), Bacillus sphaericus (Non-patent Document 7), Sporosarcina ureae (Patent Document 6), and Thermoactinomyces intermedius (Non-patent Document 8).
A reaction that converts a 2-oxo acid into an L-amino acid by the action on the 2-oxo acid of a coenzyme-regenerating enzyme and a phenylalanine dehydrogenase originating from Rhodococcus sp., Bacillus sphaericus, or Thermoactinomyces intermedius is already known (Patent Document 1, Non-patent Document 9, and Non-patent Document 10).
A reaction that converts a D-amino acid, via a 2-oxo acid or an imino acid, into an L-amino acid by the action on a racemic amino acid of bovine liver-derived glutamate dehydrogenase or Clostridium thermoaceticum-derived leucine dehydrogenase in combination with D-amino acid oxidase and a coenzyme-regenerating enzyme is also already known (Non-patent Document 10, Non-patent Document 11).    Patent Document 1: Japanese Patent Application Laid-open No. S61-146183    Patent Document 2: Japanese Patent Application Laid-open No. S63-32482    Patent Document 3: Japanese Patent Application Laid-open No. S63-304980    Patent Document 4: Japanese Patent Application Laid-open No. S59-198972    Patent Document 5: Japanese Patent Application Laid-open No. S61-239887    Patent Document 6: Japanese Patent Application Laid-open No. S63-157986    Non-patent Document 1: Journal of Bacteriology, Vol. 171(1), p. 30 (1989)    Non-patent Document 2: Journal of Synthetic Organic Chemistry, Japan, Vol. 47, No. 8, p. 749 (1989)    Non-patent Document 3: Arch. Microbiol., Vol. 169, p. 220 (1998)    Non-patent Document 4: J. of Biological Chemistry, Vol. 262(21), p. 10346 (1987)    Non-patent Document 5: J. of Biological Chemistry, Vol. 269(23), p. 16203 (1994)    Non-patent Document 6: Eur. J. Biochem., Vol. 168, p. 153 (1987)    Non-patent Document 7: Agric. Biol. Chem., Vol. 51, p. 2621 (1987)    Non-patent Document 8: J. Biochem., Vol. 109(3), p. 371 (1991)    Non-patent Document 9: J. Org. Chem., Vol. 55, p. 5567 (1990)    Non-patent Document 10: Biomolecular Engineering, Vol. 17, p. 167 (2001)    Non-patent Document 11: J. Chem. Soc.: Chem. Commun., Vol. 13, p. 947 (1990)